The overarching goal of this application, in response to PA 08-230 (Translational Research at the Aging Cancer Interface), is to develop a "bedside to bench" model of clinical and biological predictors for toxicity to adjuvant chemotherapy in older adults with breast cancer. This is important because the greatest risk factor for breast cancer is increasing age. Furthermore, the number of older adults with breast cancer is predicted to increase significantly with the aging of the US population. Several studies have demonstrated that older adults with breast cancer are at increased risk for chemotherapy toxicity;however, no standard method currently exists for identifying those individuals who are particularly vulnerable. In addition, little is known about the clinical factors, biological factors, or specific toxicities associated with reduced relative dose intensity of the prescribed chemotherapy regimen. This proposal unites the fields of geriatrics and oncology by incorporating geriatric correlates of vulnerability, and studying their impact in an aging oncology population. The specific aims of this application are: 1) to develop a predictive model consisting of clinical and biological predictors of toxicity to adjuvant chemotherapy in older adults with breast cancer;2) to understand the association between clinical and biological factors and reduced relative dose intensity (RDI) of the prescribed chemotherapy regimen;and 3) to identify the specific chemotherapy toxicities associated with reduced RDI of the prescribed chemotherapy regimen. These aims will be accomplished by a multi-disciplinary investigative team with expertise in geriatrics, oncology, and biostatistics. The team will perform a prospective, multicenter, longitudinal study of 500 adults age >70 with stage I-III breast cancer who will receive adjuvant chemotherapy. Clinical factors (geriatric assessment, sociodemographic, tumor, and treatment variables) and biological factors (renal, hepatic, and hematologic function;markers of inflammation and coagulation;and a molecular marker of aging [p16INK4a]) will be captured before chemotherapy. Patients will subsequently receive standard of care adjuvant chemotherapy as prescribed by the treating physician. Patients will be followed throughout the course of chemotherapy (from start to 1 month post-completion) to capture NCI CTCAE (v4.0) grade 3-5 toxicities. Dose delays, dose reductions, and discontinuation of treatment will also be captured, along with the relationship of these events to toxicity. With regard to expected outcomes, the current project will fill vital gaps in the knowledge about clinical and biological predictors of chemotherapy toxicity for older adults with breast cancer, areas that an oncologist should assess prior to prescribing adjuvant chemotherapy for an older adult. This proposal is innovative, as our data will ultimately be used to develop an overall risk score for toxicity. Ultimately these data will serve as the basis for future intervention studies aimed at decreasing the risk of chemotherapy toxicity and maintaining the function and health of older adults with breast cancer. PUBLIC HEALTH RELEVANCE: This proposal unites the fields of geriatrics and oncology by incorporating geriatric correlates of vulnerability and studying their impact in an aging oncology population. This study will identify clinical and biological predictors of adjuvant chemotherapy toxicity in older adults with breast cancer. These data will be used to develop a predictive equation for chemotherapy toxicity risk that can be utilized in daily oncology practice.